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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 38-42

Acute venous thromboembolism in a limited resource healthcare system: Mitigating management challenges


1 Dr. Joe Nwiloh Heart Center, St. Joseph's Hospital, Adazi-Nnukwu, Nigeria
2 Department of Internal Medicine, Cardiology Unit, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria
3 Federal Medical Center, Pediatric Cardiology Unit, Asaba, Delta State, Nigeria
4 Department of Medicine, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

Date of Submission21-Oct-2021
Date of Decision04-Dec-2021
Date of Acceptance04-Dec-2021
Date of Web Publication29-Jan-2022

Correspondence Address:
Dr. Jonathan Nwiloh
Dr. Joe Nwiloh Heart Center, St. Joseph's Hospital, Adazi-Nnukwu, Anambra State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njct.njct_12_21

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  Abstract 

Objective: The study's aim was to categorize patients' risk profiles, management options, and strategies to mitigate clinical practice challenges in a limited resource setting. Materials and Methods: We retrospectively reviewed the medical records of patients with acute venous thromboembolism (VTE) entered in a prospective database at our center from August 2014 to July 2021. Results: Twenty-two of 708 admitted patients were diagnosed with VTE for an incidence of 3.1%. The mean age was 63.7 ΁ 14.7, range 30-89, mean body mass index 31.5 ΁ 6.7 and 54.5% were female. Six (27.3%) patients had deep-vein thrombosis (DVT), 14 (63.6%) pulmonary embolism (PE) and 2 (9.1%) DVT/ PE. Dyspnea (68.2%) and leg swelling (63.6%) were the most frequent presenting symptoms. Hypoxemia with oxygen saturation <90 and cardiogenic shock was present in 27.3% and 13.6%, respectively. Due to limited access to computer tomography pulmonary angiogram (CTPA), transthoracic echocardiogram (TTE) was utilized to aide diagnosis and was performed in 14 (87.5%) patients with PE. All 14 patients showed evidence of right ventricular dysfunction, 78.5% had moderate-to-severe pulmonary hypertension and 57.1% right heart thrombus. 4 patients with DVT were treated as outpatients. All inpatients were anticoagulated with either unfractionated heparin or low-molecular-weight heparin and transitioned to Vitamin K antagonist or direct oral anticoagulant. The primary treatment duration was 3-6 months. The mean duration of follow-up was 17.5 ΁ 14.7 months. Hospital mortality was 16.7% (3/18), 30 days mortality 18.2% (4/22) and 6 months all-cause mortality 31.8% (7/22). All patients with late deaths had moderate-to-severe pulmonary hypertension. Conclusion: TTE in the absence of CTPA is a useful alternative diagnostic tool in the management of acute PE in limited-resource settings. It may also aid prognostication through estimation of pulmonary artery pressure.

Keywords: Diagnosis, echocardiogram, pulmonary embolism, sub-Saharan Africa


How to cite this article:
Nwiloh J, Orumwense N, Okoye I, Nwagbara C, Ajaegbu OC, Ozuemba BC. Acute venous thromboembolism in a limited resource healthcare system: Mitigating management challenges. Niger J Cardiovasc Thorac Surg 2020;5:38-42

How to cite this URL:
Nwiloh J, Orumwense N, Okoye I, Nwagbara C, Ajaegbu OC, Ozuemba BC. Acute venous thromboembolism in a limited resource healthcare system: Mitigating management challenges. Niger J Cardiovasc Thorac Surg [serial online] 2020 [cited 2022 Jul 2];5:38-42. Available from: http://www.nigjourcvtsurg.org/text.asp?2020/5/2/38/336863


  Introduction Top


Acute venous thromboembolism (VTE) a term inclusive of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is a major cause of morbidity and mortality and is the third most common cause of cardiovascular death after ischemic heart disease and stroke.[1] VTE is reportedly responsible for over 500,000 deaths in the European Union and 300,000 deaths in the United States per year.[2] Although the exact incidence of VTE in the United States is unclear as there is no national surveillance protocol, Silverstein and associates[3] in a 25-year VTE population-based study of 2218 patients in Olmsted County, Minnesota estimated an overall annual incidence of 117/100,000 for VTE, 48/100,000 for DVT alone and 69/100,000 for pulmonary embolus (PE) with or without documented DVT. In Africa, the epidemiology and burden of VTE are largely unknown[4] as the diagnosis is often not made premortem in many patients due to the limited diagnostic capacity seen in most hospitals. However, a recent review from Nigeria of 989 autopsies over 8 years found 29 confirmed VTE for an incidence of 2.9%.[5] The above incidence rates are all probably underestimated as PE can also present with unexplained sudden cardiac death.


  Materials and Methods Top


All consecutive adult patients 18 years and older diagnosed with acute DVT and PE over 7 years from August 2014 to July 2021 seen at our suburban 24 beds specialized heart center and entered in a prospective VTE database were retrospectively reviewed. Patients were categorized using the Wells criteria risk score for VTE.[6] The diagnostic tests performed for patients with clinical suspicion of acute VTE included but were not limited to laboratory biomarkers-Elisa D-Dimer, troponin, and CK-MB and the following imaging studies; compression ultrasonography, transthoracic echocardiogram (TTE), and computer tomography pulmonary angiogram (CTPA). These investigations however were not performed in all patients for various reasons but predominantly due to availability and financial constraints as most patients were self-pay and had no third-party health insurance coverage.

All patients received anticoagulation therapy with either unfractionated heparin (UFH), low molecular weight heparin (LMWH), Vitamin K antagonist (VKA), or direct oral anticoagulant (DOAC). Hospitalized patients were usually started on UFH or LMWH and transitioned to VKA or DOAC. The duration of primary treatment varied from 3 to 6 months.

Follow-up was through clinic visits and telephone calls made to patients or their family members.

All data were entered into an Excel spreadsheet and then imported into Sigma Plot (Systat Software, Inc., San Jose, CA, USA) for statistical analysis. Categorical variables were reported as frequencies and percentages while continuous variables were reported as mean ± standard deviations. Univariate analysis by unpaired Student's t-test with two-tailed distribution was used for continuous variables and Chi-square test or Fisher's exact test was used for categorical variables. P < 0.05 was considered statistically significant.


  Results Top


Twenty-two patients were diagnosed with VTE over the 7-year period. The mean age was 63.7 ± 14.7 years, range 30–89 years with majority (54.5%) females. The patients were mostly obese with a mean body mass index 31.5 ± 6.7. There was a total of 708 admissions over the study period for a VTE incidence of 3.1%.

The most frequent comorbidity was hypertension in 11 (50%) patients. 2 (9.1%) patients had undergone recent transabdominal gynecological surgery. Dyspnea (68.2%) and leg swelling (63.6%) were the most common presenting symptoms in about 2/3 of the patients. Tachypnea and tachycardia were present in 72.7% and 50% of patients, respectively, on admission [Table 1].
Table 1: Baseline demographics

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ELISA D-dimer was obtained in 50% of the patients and all the patients had a 12 lead electrocardiogram and at least one or more of the three imaging studies [Table 2].
Table 2: Diagnostic studies

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Overall, 6 (27.3%) patients had DVT, 14 (63.6%) PE and 2 (9.1%) DVT/PE. 4 (18.2%) patients were treated as outpatients while the remaining 18 (81.8%) were inpatients. Primary treatment in hospitalized patients was either UFH or LMWH with the transition to VKA in 54.5% and DOAC in 45.5%.

A subgroup analysis of the PE cohort is summarized in [Table 3]. Using the Wells risk score, 75% were at intermediate to high risk for PE. 14 of the 16 patients (87.5%) with PE had TTE. All 14 patients showed evidence of right ventricular (RV) dysfunction, whereas 78.5% had moderate-to-severe pulmonary hypertension on echocardiogram [Table 3]. Eight of the 14 patients (57.1%) had thrombus in the right heart and none of them had a patent foramen ovale [Figure 1]. Three patients who were hemodynamically stable underwent a CTPA. First patient had a main PA and bilateral branch embolus, second patient had bilateral PA branch embolus and the third only a branch PA embolus. 2 of these patients with markedly elevated D-Dimer also had TTE which showed RV dilatation and dysfunction with moderate pulmonary hypertension. The third patient did not have a D-Dimer or TTE performed.
Table 3: Findings in pulmonary embolism cohort

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Figure 1: (a and b) Transthoracic echocardiogram with thrombus in transit right atrium.

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6 (27.3%) patients were hypoxemic with SpO2 < 90% on room air at presentation and required supplemental oxygen therapy. An additional 5 (22.7%) patients subsequently also required oxygen for hypoxemia during their hospitalization.

3 (13.6%) patients were hypotensive with systolic blood pressure < 90 mmHg and required vasopressors. None of the patients received thrombolytic therapy. Two of the 3 patients requiring vasopressors died during the index hospitalization and 1 died suddenly at home 2 months after discharge. The observed hospital mortality was 16.7% (3/18) and occurred only in patients with PE; one died from cardiogenic shock, two from refractory hypoxemia. The 30 days mortality was 18.2% (4/22) and all-cause mortality at 6 months was 31.8% (7/22). One patient died a week after discharge at home from unknown cause, while two patients according to family members slumped suddenly at home and died 2–3 months after hospital discharge. Another patient died the following readmission at 4 months with cardiogenic shock. All three patients with late deaths after 30 days had moderate-to-severe pulmonary hypertension. The mean duration of follow-up was 17.5 ± 14.7 months. Secondary prevention treatment was not instituted in most patients.


  Discussion Top


Acute VTE is one of the three-leading causes of cardiovascular deaths after ischemic heart disease and stroke in the developed world.[1] The incidence increases with age and several studies suggest a higher incidence in blacks compared to whites and a lower incidence in Asians compared to other races.[7] Unlike in the Western World, the true incidence in sub-Saharan Africa (SSA) is not well documented with only a paucity of published data on VTE incidence and management. This is partly due to the low index of suspicion and lack of adequate diagnostic capabilities in the limited resource healthcare delivery systems seen in most of SSA. Many of these hospitals often lack the capacity to perform even the most basic diagnostic screening tests such as D-Dimer biomarker and compression ultrasonography. Elegbeleye et al.[8] in an earlier study of PE in Africans reviewed the clinical and autopsy records of 54,382 admissions and 6474 autopsies at Lagos University Teaching Hospital (LUTH) from 1966 to 1972. They found 54 cases of PE giving an incidence of 0.1%, with the most common comorbidity being congestive heart failure in 42.6% and mortality of 78%. In a more recent postmortem series of 989 autopsies at University College Hospital (UCH) Ibadan, from 1991 to 1998, Sotumbi et al.[5] found 29 confirmed VTE for an incidence rate of 2.9%. It is probable that autopsy series give a more accurate incidence, as PE is often a silent killer only identified at postmortem. This fact is illustrated in a postmortem review of 229 autopsy cases between 1989 and 1995 revealing massive or submassive PE, where the diagnosis had not been made by the Physicians in 78% of the patients.[9]

The 3.1% incidence of VTE in our clinical series is higher than the older LUTH review from over 50 years ago but comparable to the more modern era postmortem UCH series of 2.9%. The similar incidence between our premortem and the postmortem series of Sotumbi et al.[5] could probably be explained by our high clinical index of suspicion and the availability of more diagnostic tools in our armamentarium than the average hospital seen in SSA. Since patients with DVT are often asymptomatic until the onset of PE, which can manifest with variable symptoms, a high index of suspicion is crucial to initiate diagnostic tests and early treatment. The prompt commencement of anticoagulant therapy may help prevent thrombus propagation and proximal embolization to the lungs.

There have been many diagnostic algorithms proposed to facilitate risk stratification and enable quick diagnosis in patients with suspected VTE. An American College of Cardiology Expert analysis report[10] recommends first determining pretest probability using either the Wells or Geneva risk scores and then obtaining D-Dimer, with a normal level helping in ruling out PE in patients with low-to-intermediate scores. Similarly, the 2019 European Society of Cardiology (ESC) guidelines[11] also states that because of the high negative predictive value, a normal D-Dimer level makes DVT or PE unlikely.

A recent review of new imaging tools for diagnosis and management of VTE by Rahaghi et al.[12] from Brigham emphasized the pivotal role of imaging in the diagnosis of VTE, with ultrasound the gold standard for DVT. Selective pulmonary angiogram the gold standard for detecting PE has now largely been replaced by CTPA as the modality of choice. The GARFIELD-VTE registry observational study of 10,685 patients from 417 sites in 28 countries from Europe, Asia, North America, Australia, Middle East, Latin America, and South Africa, also found that in contemporary clinical practice across different continents, compression ultrasound and CT angiography represent the standard of practice for the diagnosis of DVT and PE, respectively.[13]

Unfortunately, these diagnostic imaging tools are not readily available in most hospitals in SSA, therefore often posing a premortem diagnostic and therapeutic challenge for many patients.[14],[15] CTPA for instance is not readily accessible within a few miles radius to facilitate PE diagnosis in most hospitals. Even when available, financial constraint often prevents access by many patients. In other to overcome some of these diagnostic dilemmas, we have had to modify the guidelines by adopting more easily available diagnostic tools such as echocardiogram despite their known limitations. Although echocardiogram may detect RV pressure overload and dysfunction that can result from acute PE, the criteria for PE diagnosis have varied in different studies. Therefore because of the reported negative predictive value of 40%–50%, a negative result does not rule out a PE. Consequently, the ESC guidelines do not mandate an echocardiogram as part of the routine workup in hemodynamically stable patients with suspected PE. However, with hemodynamic instability suggestive of massive PE, bedside echocardiogram or emergency CTPA depending on availability is recommended for diagnosis.[11] Therefore, given the lack of CTPA at our center, we have routinely used the echocardiogram in patients with high risk for PE to identify possible surrogate markers. There is also the added benefit of obtaining pulmonary artery systolic pressure which has prognostic value as the long-term objectives of VTE treatment include reducing the incidence of chronic thromboembolic pulmonary hypertension and postphlebetic syndrome with their known sequela.

Amongst our 14 patients with PE who underwent TTE, 100% demonstrated signs of RV dysfunction, 78.5% had moderate-to-severe pulmonary artery hypertension and 57.1% had right heart thrombus. Mobile heart thrombi are reportedly detected by imaging in <4% of unselected patients with PE, with an increase to 18% among ICU patients with PE.[11] The significantly higher 57.1% incidence of right heart mobile thrombi in our series may partly be explained by the routine rather than the selective use of echocardiogram as recommended by the guidelines. Two of the three patients who underwent a CTPA also had a TTE which was suggestive of submassive PE with RV dilatation/dysfunction and moderate pulmonary hypertension.

Therefore, considering the lack of accessibility to CTPA for most patients suspected at high risk for PE in SSA, TTE when available may provide a reasonable alternative to aide diagnosis and guide therapy. The ESC guidelines state that there is justification for emergency thrombolytic therapy in hemodynamically compromised patients (massive PE) and unequivocal signs of RV pressure overload, i.e. 60/60 sign, McConnell sign (RV free wall akinesis sparing the apex) or right heart thrombi.

However in patients with submassive PE (echo evidence of RV dysfunction but without hemodynamic compromise) the American Society of Hematology (ASH) 2020 guidelines recommends treatment with anticoagulation alone over routine use of thrombolysis in addition to anticoagulation.[7] Fortunately, the number of patients requiring thrombolytic therapy is relatively small in the reported series. Because of the myriad range of PE presentations, treatment can vary depending on the case complexity and institutional resources and available expertise. Anticoagulation remains the mainstay of treatment for most PE patients. Other treatment modalities include systemic thrombolysis, catheter-directed thrombolysis or embolectomy, surgical embolectomy, and mechanical circulatory support with venoarterial extracorporeal membrane oxygenator (ECMO). The ASH 2020 guidelines suggest that in patients with extensive DVT considered appropriate for thrombolysis, catheter-directed thrombolysis is preferred over systemic thrombolysis if local expertise is available. While for patients with PE considered appropriate for thrombolysis, systemic thrombolysis is suggested over catheter-directed thrombolysis.[7] At our center, the only treatment options previously available were anticoagulation and systemic thrombolysis, until recently when we acquired the capacity for ECMO. Fortunately, many patients with PE can be managed without more advanced and invasive therapies. In the GARFIELD-VTE registry observational study, the treatment was anticoagulation therapy alone in 90.9%, thrombolytic ± surgical/mechanical therapy 5.1%, and no therapy in 4.0%.[13]

The mortality in our series was within the reported range, with the three deaths occurring in one patient from cardiogenic shock and 2 patients from refractory hypoxemia, all suggestive of massive PE. None of these patients however received thrombolytic therapy which may have influenced their outcome. However following this review, in line with the current ASH 2020 guidelines, we intend to be more aggressive with the use of systemic thrombolysis in the presence of clinical and echocardiographic evidence suggestive of massive PE. The 3 late deaths after 30 days were sudden in 2 patients occurring at 2 and 3 months respectively and the third patient was readmitted at 4 months with cardiogenic shock. All three patients had moderate to severe pulmonary hypertension at initial diagnosis suggesting that this might be a prognosticator for poor outcome. Lloyd-Jones et al.[16] report that of those patients who experience a first VTE, approximately 20% present with sudden death secondary to PE, approximately 30% have died within 30 days and approximately 30% develop recurrent VTE within 10 years. On completion of the 3–6 months of primary treatment, we did not continue with secondary prevention except in patients with other indications for anticoagulation such as atrial fibrillation.

Although VTE is common, it is a preventable cause of death. As a result of the increasing knowledge of pathophysiology and known predisposing risk factors for VTE, the institution of a combination of prophylactic pharmacologic and mechanical measures has helped reduce the incidence in hospitalized medical and surgical patients.

The adage that an ounce of prevention is worth a pound of cure is certainly applicable to VTE, and so all our hospitalized patients without a contraindication to anticoagulation are placed on prophylactic VTE pharmacologic regimen.


  Conclusion Top


With a high Wells pretest risk score, elevated D-dimer ± positive compression ultrasonography, we routinely use TTE to aid diagnosis of PE in the absence of CTPA in our limited resource center.

Study limitations

This is a single institution retrospective review with relatively small numbers. However, given the paucity of reported VTE series from SSA, a meta-analysis with other reported reviews may help elucidate further the epidemiology and management of this potentially fatal but often undiagnosed condition premortem in SSA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007;98:756-64.  Back to cited text no. 1
    
2.
Heit JA, Cohen AT, Anderson FA. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood 2005;106:910.  Back to cited text no. 2
    
3.
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ. Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25 year population based study. Arch Intern Med 1998;158:585-93.  Back to cited text no. 3
    
4.
Danwang C, Temgoua MN, Agbor VN, Tankeu AT, Noubiap JJ. Epidemiology of venous thromboembolism in Africa: A systematic review and meta-analysis protocol. BMJ Open 2017;7:e016223.  Back to cited text no. 4
    
5.
Sotumbi PT, Idowu AT, Akang EU, Aken Ova YA. Prevalence of venous thromboembolism at post-mortem in an African population: A cause for concern. Afr J Med Sci 2006;35:345-8.  Back to cited text no. 5
    
6.
Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83:416-20.  Back to cited text no. 6
    
7.
Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020;4:4693-738.  Back to cited text no. 7
    
8.
Elegbeleye OO, Femi-pearse D. Pulmonary embolism in Africans. Trop Geogr Med 1975;27:31-3.  Back to cited text no. 8
    
9.
Morpurgo M, Schmid C, Mandelli V. Factors influencing the clinical diagnosis of pulmonary embolism: Analysis of 229 postmortem cases. Int J Cardiol 1998;65 Suppl 1:S79-82.  Back to cited text no. 9
    
10.
Bernal AG, Fanola C, Bartos JA. Management of PE. Expert Analysis. Available from: https://Acc.org/latest-in-cardiology/articles/2020/01/27/07/42/management-of-pe. [Last accessed on 2021 Nov 19].  Back to cited text no. 10
    
11.
Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonaryembolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Heart J 2020;41:543-603.  Back to cited text no. 11
    
12.
Rahaghi FN, Minhas JK, Heresi GA. Diagnosis of deep venous thrombosis and pulmonary embolism: New imaging tools and modalities. Clin Chest Med 2018;39:493-504.  Back to cited text no. 12
    
13.
Ageno W, Haas S, Weitz JI, Goldhaber SZ, Turpie AG, Goto S, et al. Characteristics and management of patients with venous thromboembolism: The GARFIELD-VTE registry. Thromb Haemost 2019;119:319-27.  Back to cited text no. 13
    
14.
Kotila TR, Fasola FA, Busari EO. A revisit of venous thromboembolism. Afr J Med Med Sci 2013;42:177-81.  Back to cited text no. 14
    
15.
Kesieme EB, Okokhere P, Eluehike S, Isabu P. Challenges in the management of iliofemoral deep vein thrombosis in a resource limited setting: A case series. Pan Afr Med J 2014;18:254.  Back to cited text no. 15
    
16.
Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, de Simone G, et al. Heart disease and stroke statistics -2010 update: A report from the American Heart Association. Circulation 2010;121:e46-215.  Back to cited text no. 16
    


    Figures

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    Tables

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